Few studies have used precise age-specific data to construct age-standardized estimates of the relative risks (RRs) of COVID-19 mortality for people experiencing homelessness (PEH) vs the general population, and none to date has addressed race and ethnicity and sex variations in COVID-19 mortality among PEH with COVID-19 infection. To measure age-standardized mortality rate ratios for PEH vs the general population overall and by sex and race and ethnicity. In this cross-sectional study, crude and age-specific COVID-19 mortality rates per 100 000 people were calculated using 5-year age groups and standardized mortality ratios for PEH and the general population aged 25 years and older, assessing differences by race and ethnicity and sex, from January 1, 2020, to November 1, 2021. Mortality and population estimates came from COVID-19 mandatory case reporting conducted by the Los Angeles County Department of Public Health, the annual point-in-time homeless count, and the US Census. The main outcome was COVID-19 deaths sourced from clinician reports, death certificates, medical examiner reports, and vital records deaths. PEH status was determined using the US Department of Housing and Urban Development definitions for homelessness at the time of COVID-19 diagnosis or symptom onset. The study population included 25 441 deaths among an estimated 6 382 402 general population individuals and 256 deaths among an estimated 52 015 PEH. The race and ethnicity of the PEH sample was as follows: 15 539 Black (29.9%), 18 057 Hispanic (34.7%), 14 871 female (28.6%), 37 007 male (71.3%), and 3380 aged 65 years or older (6.5%), compared with the estimated general population of 6 382 402, which was 591 003 Black (9.3%), 2 854 842 Hispanic (44.7%), 3 329 765 female (52.2%), 3 052 637 male (47.8%), and 1 190 979 aged 65 years or older (18.7%). Crude death rates were 0.49% for PEH and 0.40% for the general population, but PEH experienced age-specific COVID-19 mortality risk 2.35 (95% CI, 2.08-2.66) times higher than the general population. There was significant risk associated with PEH status compared with their counterparts in the general population for Black PEH (RR, 1.69; 95% CI, 1.31-2.18), Hispanic PEH (RR, 2.34; 95% CI, 1.96-2.79), White PEH (RR, 8.33; 95% CI, 6.37-10.88), female PEH (RR, 3.39; 95% CI, 2.56-4.48), and male PEH (RR, 1.74; 95% CI, 1.52-2.00). This cross-sectional study of COVID-19 mortality among PEH with COVID-19 infection provides evidence suggesting excess risk of age-adjusted COVID-19 mortality among PEH compared with the general population. This study furthers understanding of the intersectional association between homelessness and race and ethnicity, as higher levels of mortality but narrower racial disparities among PEH than in the general population were observed.